Rationale I :For TDM1 to be active, the presence of an intact HER2 receptor is "key" since the internalization of the cytotoxic moiety depends on the binding of trastuzumab to the external domain of HER2.

negative predictive value of the 89Zr-trastuzumab PET/CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The primary objective is to show that pre-treatment 89Zr-trastuzumab PET/CT is able to select lesions not responding morphologically from treatment with T-DM1 (applying RECIST 1.0 criteria).

Secondary Outcome Measures:

negative predictive value of the early FDG PET/CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The first secondary objective is to show that early FDG PET/CT (performed after one cycle of T-DM1 just before the second cycle) is able to select lesions not responding from treatment with T-DM1 according to metabolic and morphological response criteria post 3 cycles of T-DM1.

negative predictive value of the 89Zr-trastuzumab PET/CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The second secondary objective is to show that 89Zr-trastuzumab PET/CT is able to select lesions not responding from treatment with T-DM1 according to metabolic response criteria post 3 cycles of T-DM1.

negative predictive value of the combined 89Zr-trastuzumab PET/CT and early PET/CT [ Time Frame: 2 years ] [ Designated as safety issue: No ]

The third secondary objective is to show that a lesion with no/faint uptake on 89Zr-trastuzumab PET/CT and not responding metabolically on the early FDG-PET/CT will not respond according to metabolic and morphological criteria after 3 cycles of T-DM1.

After an imaging phase, the patient will receive T-DM1 iv every 3 weeks until progression or toxicity

Drug: T-DM1

3.6 mg/kg iv every 3 weeks

Other Name: Trastuzumab-DM1

Procedure: 89Zr-trastuzumab

Injection of 89Zr-trastuzumab for HER2 imaging

Other Name: Zirconium 89 labelled trastuzumab

Detailed Description:

The main objective of the trial is to prospectively evaluate the ability of a zirconium 89 labelled trastuzumab PET, to predict, before initiation of the treatment, treatment failure to a new targeted drug: T-DM1.

At the same time, the early FDG-PET/CT, performed after 1 course of T-DM1, will also evaluated for its ability to predict non response to TDM1.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

The patient must have histologically confirmed HER2 positive invasive carcinoma of the breast in the reference laboratory of the participating center. HER2 positive criteria to be applied are those used in the participating countries:

The Netherlands: IHC 3+ or FISH ratio ≥ 2 in the reference laboratory of the participating center

The patient must have documented progressive disease and present with at least 2 non-bone "target" metastatic lesions, unequivocally of neoplastic origin with

a transaxial diameter greater than 2 cm on the screening diagnostic CT/MRI for all non-bone lesions except lymphnodes

a short axis greater than 1,5 cm for lymphnodes on the screening diagnostic CT/MRI These two lesions should not be confluent with adjacent lesions and not have been irradiated previously.

A concurrent biopsy of a metastatic site is mandatory (with two formalin fixed paraffin embedded (FFPE) core sample and two snap frozen tumor sample) after progression has been documented and before inclusion and the patient agrees with the procedure.

Primary tumor blocks (or 11 unstained slides) available for confirmatory central laboratory HER2 testing in Institut Jules Bordet. If available, a snap frozen sample of the primary tumor will also be centralized in Institut Jules Bordet.

International normalized ratio (INR) and activated partial thromboplastin time or partial thromboplastin time (aPTT or PTT) < 1.5 x ULN (unless on therapeutic anti-coagulation except vitamin K antagonists which are prohibited in this study)

Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.

For women of childbearing potential a serum pregnancy test will be done (and it must be negative) and an agreement to use a highly-effective form of contraception during all the study and at least the following 7 months will be obtained.

Signed written informed consent obtained prior to any study specific procedure.

Patients with brain metastasis as the sole site of metastatic disease and/or are symptomatic or require therapy to control symptoms NB: Brain metastasis are allowed provided they are asymptomatic and/or controlled by previous radiotherapy. In case of recent prior brain radiotherapy, there must be evidence on MRI imaging of brain metastatic control for at least 6 weeks since the end of radiotherapy. Moreover, the patient should be at the end of corticosteroid therapy and be clinically asymptomatic.

History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned

Patient who received lapatinib within the 15 days prior to 89Zr-Trastuzumab injection

Patient under a prohibited concomitant therapy, including vitamine K antagonist

Patients with a peripheral neuropathy Grade 3 or higher

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565200